The overall goal of this program project is to study specific pathophysiologic mechanisms underlying common neonatal lung disorders. The response of the immature or developing lung to acute injury and reparative phenomenon will be studied utilizing animal models of disease. The program consists of four projects and two cores and will bring together a large number of investigators with expertise in several disciplines to focus on mechanisms of lung damage in repair. The long range goal is to improve current methods of treatment and prevention of HMD and improve methods of treatment in other common lung disorders in order to prevent the common complication of bronchopulmonary dysplasia, a disorder of premature infants with catastrophic consequences. This program project will extend the studies currently funded through the pulmonary SCOR program. The projects focus on four main objectives: 1. to understand the mechanisms of sequential lung injury in hyaline membrane disease (HMD) and mechanisms of normal and abnormal recovery (Project 1), 2. to study mechanisms of pulmonary host defenses in the neonate, including cellular immunology and organ response to infection (Projects 2 and 3), 3. to investigate mechanisms controlling the pulmonary circulation in the neonate and factors regulating gas exchange during acute and convalescent stages of lung injury (Projects 1 and 3), 4. to define features unique to the neonate in the development of respiratory failure and the physiologic handicaps of the neonate in responding to respiratory failure. The combined projects share common goals and depend upon common use of core animal, physiologic, biochemistry and electron microscopic facilities and support personnel within the Administrative and Research Resources Core.